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Publication Number
US-11427800-B2
Publication Date
2022-08-30
Expiration Date
Abstract
It can be useful to regulate the growth of microbial cells. Some embodiments herein provide genetically engineered microbial cells that can produce bacteriocins to control the growth of microbial cells. In some embodiments, microbial cells are contained within a desired environment. In some embodiments, contaminating microbial cells are neutralized. In some embodiments, a first microbial cell type regulates the growth of a second microbial cell type so as to maintain a desired ratio of the two cell types.
Core Innovation
The invention relates to genetically engineered microbial cells that express a secreted bacteriocin to inhibit or prevent reproduction of at least one of the genetically engineered microbial cell or a second microbial cell. A first nucleic acid encodes the secreted bacteriocin under a first promoter, and a second nucleic acid encodes an immunity modulator that protects against the secreted bacteriocin.
The engineered cell is genetically engineered to decrease or eliminate at least one of transcription, post-transcriptional expression, or post-transcriptional activity of the immunity modulator concurrent with expression of the secreted bacteriocin. This coordinated decrease or elimination causes the secreted bacteriocin to inhibit or prevent reproduction of the genetically engineered microbial cell.
The disclosure further supports promoter-mediated regulation and other genetic control architectures for decreasing or eliminating immunity modulator function while bacteriocin expression occurs. Additional embodiments include additional secreted bacteriocins, cis arrangement of nucleic acids, and relationships controlled by a promoter.
Claims Coverage
The independent claim set centers on one independent claim, clm-00001, requiring a secreted bacteriocin expression module and an immunity modulator module, with immunity modulator function decreased or eliminated concurrent with secreted bacteriocin expression so that the bacteriocin inhibits or prevents reproduction of the engineered cell. Dependent features add cis arrangement, additional secreted bacteriocins, host species limitations, and a different second microbial cell.
Secreted bacteriocin expression to inhibit reproduction
A first nucleic acid under the control of a first promoter encodes a secreted bacteriocin capable of inhibiting or preventing reproduction of at least one of the genetically engineered microbial cell or a second microbial cell.
Immunity modulator protection encoded in a second nucleic acid
A second nucleic acid encodes an immunity modulator that protects against the secreted bacteriocin.
Concurrent decrease or elimination of immunity modulator activity
The genetically engineered microbial cell is engineered to decrease or eliminate at least one of transcription, post-transcriptional expression, or post-transcriptional activity of the immunity modulator concurrent with expression of the secreted bacteriocin, thereby causing the secreted bacteriocin to inhibit or prevent reproduction of the genetically engineered microbial cell.
Cis arrangement of nucleic acids
A third nucleic acid is arranged in cis with a first nucleic acid.
Additional secreted bacteriocin and target
A third nucleic acid encodes a second secreted bacteriocin capable of inhibiting or preventing reproduction of a third microbial cell.
Enumerated microbial host species set
The genetically engineered microbial cells are selected from a set comprising Bacillus species, Paenibacillus species, Streptomyces species, Micrococcus species, Corynebacterium species, Acetobacter species, Cyanobacteria species, Salmonella species, Rhodococcus species, Pseudomonas species, Lactobacillus species, Enterococcus species, Alcaligenes species, Klebsiella species, Arthrobacter species, Brevibacterium species, and Thermus aquaticus, including Pseudomonas stutzeri, Clostridium thermocellus, and Escherichia coli.
Target microbial cell is different species or strain
The second microbial cell is a different species or strain from the genetically engineered microbial cell.
The claims are directed to a genetically engineered microbial cell that expresses a secreted bacteriocin and an immunity modulator, while the immunity modulator is decreased or eliminated in transcriptional, post-transcriptional expression, or post-transcriptional activity concurrent with bacteriocin expression so that the bacteriocin inhibits or prevents reproduction of the engineered cell.
Stated Advantages
Enables the secreted bacteriocin to inhibit or prevent reproduction of the genetically engineered microbial cell while an immunity modulator is present.
Provides controlled growth of genetically engineered microorganisms using bacteriocins with reduced or eliminated immunity concurrent with bacteriocin expression.
Supports maintaining desired cell-type ratios and protecting against invasions as described.
Allows additional bacteriocin production and reengineering to respond to changes in a culture as described.
Enables spatial separation in systems so bacteriocins enter without allowing microorganisms to migrate, as described.
Supports feedstock storage with bacteriocin-producing organisms in fluid communication but physically separated, as described.
Documented Applications
Systems/devices for spatial separation of environments so bacteriocins enter without microorganisms migrating, as described.
Kits of strains for different bacteriocins, as described.
Detection/diagnostic method using regulatable promoters responsive to molecules, as described.
Culture operation over extended periods with detection of changes such as new invading organisms and reengineering to respond by producing additional bacteriocins, as described.
Feedstock storage using bacteriocin-producing organisms in fluid communication but physically separated, as described.
Protecting against invasions and maintaining a desired ratio of cell types in a population of cells, as described.
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